The field of the invention relates to compositions and methods for localized and sustained delivery of drugs when it is desirable to keep the drugs confined to a specific body space to enhance their therapeutic action and minimize cost and non-essential exposure. In particular, the field of the invention relates to compositions and methods for localized and sustained delivery of water-soluble synthetic compounds, as well as synthetic lipophilic compounds typically <1,000 Mol. Wt., as well as localized and sustained delivery of larger hydrophilic therapeutic agents such as peptides, proteins and nucleic acids.
Major blinding diseases such as exudative “wet” macular degeneration (AMD), and diabetic retinopathy are caused by excessive pathologic capillary sprouting beneath the retina, damaging retinal layers above. Anti-angiogenic proteins including Avastin, Lucentis and Eyelea, all of which neutralize angiogenic VEGF, slow progress of neovascular eye disease, but must be injected into patient vitreous humor (VH). VH fills most of the eye, is viscous and contains natural polymers with multiple negative charges. Therapeutic proteins move through and out of the eye with half-lives of 4-8 days, they must be re-injected at 1-2 month intervals to sustain efficacy. Frequent injection is a great clinical burden, is painful, and increases risk of retinal detachment and infection. Nano-technology involving entrapment or binding of the proteins into transparent degradable particles has been attempted by many labs seeking continuous release of the injected agent to decrease injection frequency, an approach also applied to small synthetic drugs. Typical carriers are large particles (>1 micron), are difficult to sterilize), they move slowly through viscous ocular fluid, or may be smaller and anchored via stable multi (+)charges. Particles may exit the eye intact or may break down to yield fragments which can be toxic or inflammatory, none has yet been approved for the delivery of proteins or peptides.